rs5748489

Positions:

• chr22-19939623-A-C
• chr22-19939623-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006440.5(TXNRD2):​c.103+2078T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,996 control chromosomes in the GnomAD database, including 29,977 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29977 hom., cov: 31)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

TXNRD2 (HGNC:18155): (thioredoxin reductase 2) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNRD2	NM_006440.5	c.103+2078T>G		intron_variant		ENST00000400521.7	NP_006431.2
TXNRD2	NM_001282512.3	c.103+2078T>G		intron_variant			NP_001269441.1
TXNRD2	NM_001352300.2	c.103+2078T>G		intron_variant			NP_001339229.1
TXNRD2	NR_147957.2	n.118+2078T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7	c.103+2078T>G		intron_variant		1	NM_006440.5	ENSP00000383365	P4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94578 AN: 151878 Hom.: 29924 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94691 AN: 151996 Hom.: 29977 Cov.: 31 AF XY: 0.623 AC XY: 46308 AN XY: 74276

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.664

Alfa AF: 0.600 Hom.: 4317

Bravo AF: 0.640

Asia WGS AF: 0.679 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5748489; hg19: chr22-19927146;